Knee Osteoarthritis Outcome Measures in Arthritic Patients With Osteoporosis

The traditional treatment paradigm for osteoarthritis (OA) involves palliative strategies
focused on pain management and joint replacement. The longstanding inability to develop
disease-modifying therapies that can rejuvenate joint cartilage is a great unmet need
considering that diarthrodial and spinal OA is the most prevalent disease in the US, equal in
numbers to the next top 4 disorders combined (heart, pulmonary, mental health and diabetic
conditions) (CDC, 2009). Thus, the development of an effective remittive treatment for OA is
a vital public health initiative with potential for tremendous impact. Our long-term research
objective is to test a radically different strategy for treatment of OA that is based on
findings recently published in Science Translational Medicine (Sampson et al., 2011) that
identified human parathyroid hormone1-34 (teriparatide) as a chondroregenerative agent in a
murine model of OA. Suggesting a parallel effect in human OA, data mined from the
NIH-sponsored OA Initiative revealed improved WOMAC knee function scores in arthritic
subjects coincidentally prescribed teriparatide (trade name: Forteo®) to treat osteoporosis.
These preclinical and human data provide compelling rationale to study Forteo® as a novel OA
therapy directed at improving joint structure and function. The central aim of our overall
research program is to challenge the paradigm that cartilage loss in OA is irreversible.
Thus, our long-term programmatic goal is to test Forteo® as the first and only
disease-modifying treatment for OA with potential to rapidly impact clinical care. To achieve
this, we have been developing a clinical trial where subjects with medial compartment
Kellgren Lawrence (K-L) stage II-III knee OA will receive either Forteo® or Prolia® (a brand
of denosumab) for two years. Disease progression will be assessed via structural, biomarker
and functional outcomes at various time points out to 24 months post-initiation of therapy.
Since Forteo® is a widely used therapeutic in patients with osteoporosis (OP)-related severe
bone loss, we propose to examine OA outcomes in OP patients with concomitant knee OA. This
pilot study described here that tests the hypothesis that patients with unilateral or
bilateral knee OA (Kellgren-Lawrence grade II-III) that are prescribed Forteo® to treat their
primary diagnosis of OP will demonstrate improved physical function (Timed-Up-And-Go),
improved patient-reported outcomes (PROMIS 12a, v1.0), and increased blood levels in the
cartilage anabolic marker type II collagen C-propeptide. Completion of this proposed
experimental design would provide critical proof-of-concept preliminary data supporting the
use of biomarkers, physical function testing and questionnaire-based functional assessment to
study OA in patients.

INCLUSION CRITERIA:

- Age: 40-80 years (inclusive)

- Gender: male or female (non-pregnant)

- Fluent in written and spoken English

- Patients capable of giving informed consent

- Primary diagnosis of osteoporosis that will be treated with either Forteo® to induce
bone anabolism or Prolia® by the study investigator as part of patient's standard of
care treatment

- Symptomatic, medial compartment knee OA with a Kellgren-Lawrence (K-L) score between
II-III (documented in the medical record by previously collected knee series
radiography). Radiographs to be performed within past two years.

EXCLUSION CRITERIA:

- Age < 40 or >80 years

- Cognitive impairment

- Pregnancy

- Non-English speaking persons

- History of hyperparathyroidism, hypercalcemia, current/recent renal stones, or
malignancy

- Depression (currently taking home medication)

- History of inflammatory disease (colitis, rheumatoid arthritis, psoriasis, lupus,
scleroderma, spondylitis)

- Use of immunosuppressants, chemotherapy, or radiotherapy

- BMI, angular deformity and K-L score of the contralateral knee (if the OA is
bilateral) will be noted as covariates